I'm Dave. In 2002, I got sick. I didn't get better after a couple of weeks so I went to see a doctor, which I almost never do, because I'm a physician, too. When I found out that I had an incurable leukemia, I began recording my thoughts and emotions about the disease, and sending them to my family and friends in a series of messages we called "Dave's Great Adventure." I'm having more therapy so I'm resurrecting my old DGA messages, adding new messages and putting them in blog form this time.

About Me

Wednesday, January 18, 2012

[[[ “If you want to make God laugh, tell Him your plans.” --Anonymous I’ve used this quote a couple of times over the years but it’s again appropriate. We only “think” we have our lives planned out. The following message was started in mid-November, but then I didn’t get back to it for quite a while. Meanwhile, things have changed again. Read on. ]]]

---November 14, 2011---I think there are real signs of hope with this new stuff. I believe it’s working better than I thought it might.

When I last wrote about what was going on I had just finished Phase One of my Arzerra (ofatumumab) treatments. The treatments had begun rather abruptly in August. In mid-August, after waiting five weeks to hear the results of the cytogenetic tests which I described in excruciating detail in my last letter, my local doc got the details about the development of my worrisome p53 mutation and the plan for treatment, from my doc in Houston. With that information, we began the Arzerra almost immediately, within a week. In fact, we started the first dose of the Arzerra on August 23rd, our 42nd wedding anniversary. I try to make our anniversaries memorable for Kathy.

The Arzerra infusions have gone very well. The first phase of the treatment was eight weekly infusions. The side effects have been relatively minimal, all things considered, and that’s because I haven’t been getting any poisons this time. With all my previous treatments I had combinations of drugs which included poisons, as most chemotherapy targets fast growing cells, like cancer cells. The problem is, of course, that all fast-growing cells in one’s body are not cancer cells, so normal cells get affected as well. And that leads to side effects; the nausea, hair loss, mouth sores, etc. One of the drugs which I had in all three previous chemotherapy regimens is some stuff called cyclophosphamide, which advertises its role in chemotherapy by its trade name, Cytoxan. That’s a play on its activity within the body. “Cyto-” means cell; “toxin” means poison. Therefore, its trade name, Cytoxan, or “cyto-toxin” literally means “cell poison.”

But the Arzerra I’m now getting is not a poison, per se. It is pure antibody, an antibody directed against white blood cells with a protein called CD20, which is on the cell membrane of all CLL cells (CLL cells are actually abnormal B-lymphocytes, which are the kind that make your antibodies). It attaches to the CD20 protein and allows the body’s immune system to bore a hole in the leukemia cell’s membrane, popping it rather like a microscopic balloon. That’s the good or even great part about the antibody treatments. They target only a specific population of cells, ignoring the rest. But when they simultaneously pop billions of leukemia cells, all those dying cells spill their cell contents into your blood stream, and all those proteins, histamines, DNA and such, can clog your kidneys, cause severe allergic reactions, breathing problems, low blood pressure, and the like. Because of this possibility, before each treatment we are given antihistamines and steroids, to suppress the allergy-like reactions, and we are given the drug very, very slowly. The first treatment I got took us from 8:30 in the morning until 6:30 in the evening to complete. As I got used to the drug and as my white blood cell counts dropped (giving the Arzerra ever fewer “targets” to seek out), we were able to start giving the drug faster and faster and by the end of my eight consecutive weeks of treatments, we were able to complete the infusions by 3:00PM.

By the way, my clinic billed about $25,000 for each weekly treatment. These newer chemotherapy drugs are wonderful but they are also fantastically expensive.

But the Arzerra has worked extremely well, dropping my white blood cell counts from a pre-treatment level of just under 80,000 (normal is about 3,000 to about 9,000) to about 4,000 after the eight weeks of treatment. Now, that count is in the normal range, but the count still is not “normal,” as another test that looks for abnormal white cells in my blood, determined that 35% of my remaining white blood cells were still leukemia cells. But that’s not really a surprise. The Arzerra really wasn’t expected to put me into a complete remission anyway.

Despite that minor point, things are going very well, better than I’d hoped. When I started the Arzerra I was told that there was only about a 50% chance I would have a response to the drug because I now have the more aggressive leukemia mutation. Well, I’m obviously in the 50% of the population on whom the new drug works. Then, after we finished the eight consecutive weeks of infusions, and waited a full four weeks for the start of my monthly treatments, my white counts continued to drift down. In other words, despite stopping the drug for a month, my disease didn’t come charging back. I hope this trend continues. So far it has. I’ve had one of the monthly infusions and my white counts have remained around 3,000 or so. My next treatment will be in early December and will continue monthly through next February.

But just about any treatment will have side effects, and the major side effect that one gets with the Arzerra stems from its ability to seek out and kill only white blood cells with the CD20 marker on its cell wall. Unfortunately, all NORMAL B-lymphocytes (the ones we depend on to make our antibodies) ALSO have the CD20 antigen. So, that means that while the Arzerra is wiping out billions of leukemia cells, it’s also taking out a large number of my normal lymphocytes, too. That puts me at risk for infections as well as other tumors and so forth. But, that’s the chance I have to take to be able to hold my disease at bay long enough to try to find another, better, long term treatment and possibly a cure. In any case, the plan all along with the Arzerra has been to give me this drug over about six months, then wait perhaps six more months until it stopped working and then do…something. What, exactly, has been unclear.

I’ve been trying to re-evaluate my expected longevity based on the results of the Arzerra so far. When I first found out I had the p53 mutation, which I already knew was bad, I went back to my sources, one of which is an excellent CLL web based resource called “CLL Topics,” a well researched, critical review of all things related to CLL and its treatment. Here I found the article which noted that average longevity was just 13 to 15 months! Just over a year. But, it’s now been six months since I started the Arzerra and things seem to be going well. Since the CLL hasn’t stormed back between my monthly infusions so far, I’m guessing I may have more than a year left after all. Other sources I’ve checked suggest average longevity is perhaps 1 to 2 years and another source says 2 to 3 years. In any case, if these are accurate, those are AVERAGE numbers meaning half the patients will live longer, the other half less than that. And all of us cancer patients just KNOW we’re going to be in the longer-lived half. It’s unclear also, if these numbers are for treated or untreated patients, and if treated, what the treatment was. We shall see. In any case, I’m feeling much too normal to think that I’ll be dead within the year.

---January 11, 2012--- Things have changed. I wrote all the above about eight weeks ago but then couldn’t get back to it to finish the report. I had been very encouraged by the results of the Arzerra treatments since they seemed to be holding off the advancement of the disease. But, in the last several weeks, though my lab tests still show improvement, my lymph nodes are again enlarging in my armpits and some are now growing in my neck as well. Not good. My local oncologist here in Denton recently reported this to Dr. Keating, my doc in Houston at M. D. Anderson, and we got an unexpected phone call a few days ago.

Dr. Keating called back with some surprising and potentially very exciting news. He has cancelled the last of my four monthly infusions of Arzerra, since it hasn’t worked all that well in the last couple of months anyway and, after I’ve been off the drug for a month, which will be at the end of January, I am to get in contact with him again to talk about enrolling in a clinical study of some kind. What kind of clinical trial? I don’t yet know. When will it start? I don’t know. How long will it be? I don’t know. What are the risks involved? I don’t know.

He had been talking about possibly going to a stem cell transplant in the very near future. In fact, I have several appointments set up in late February to speak to the transplant team in Houston. That seems to be the new approach to treating folks with the p53 mutation. Rather than try multiple treatments of chemotherapy which will likely not work, they’re going to transplantion sooner in the course of treatment, as the transplant works better when done in patients who are not critically ill. Of course, with a 15 to 25% mortality rate associated with transplant, it’s a hard sell to folks who don’t feel or look critically ill, but that’s the current trend and I have been rather expecting to be going that direction in the near future.

But, now Dr. Keating is talking about enrolling me in a clinical trial which is just now opening. Unfortunately for me, the message I received did not mention what the trial would be, so I’m a bit in the dark. We have talked about the new, rather unfortunately named “btk inhibitors” like CAL 101 and PCI 32765 (this would be a good time to use Google!) which is what I am hoping he’s going to get me into. These seem to have great promise in destroying the disease and seem to have minimal side effects. The treatment consists of simply taking a pill daily, with most patients having minimal side effects. That sounds too good to be true. I mentioned the unfortunate naming…. The drugs are called “Bruton’s tyrosine kinase inhibitors,” hence the “btk” designation. But not too many years ago there was a serial killer in Wichita, Kansas who went by the name of the “BTK killer,” for “Bind, Torture, Kill.” Well, this stuff kills CLL cells, I suppose. Maybe it tortures them too!

Other possibilities for the clinical trial include a combination of drugs using lenolidamide, a derivative of the notorious birth defect causing drug Thalidomide. It is also a pill form of anti-CLL drug, but is frequently used in combination with other drugs such as Arzerra. And then there are the new CARs treatments. This stands for “Chimeric Antigen Receptors” and is the basis for the treatment that made a big splash in the press last summer, as having cured a few patients. It involves treating one’s own T-lymphocytes and training them to attack the leukemia cells. This has worked well in a very few patients, but thus far there is no long term follow-up, just a year or so. It may take the place of stem cell transplants some day, but is extremely labor intensive and expensive, since it involves taking a patient’s T-lymphocytes out, treating then, and reinjecting them into the same patient. Every patient will have to have a personalized treatment with his/her own T-lymphocytes. My cells wouldn’t work for someone else, and vice versa. More about T-lymphocytes later, if I end up in that kind of program.

Or, the clinical trial could be something else entirely. The message I got was third hand, having gone from Dr. Keating to my local doc’s message machine and then passed to my doc’s nurse, who called me. If there were more details in the message, I didn’t get them. I’ve sent a message to my team in Houston asking for more information but have yet to hear back from them. Wish me luck.

And so, that’s the latest. My disease is getting aggressive again, the Arzerra isn’t working as well, and now I’m off it entirely. And, some experimental medicine looms in my future, probably within a month or so.

But despite all this, I’m still doing pretty well. I don’t feel ill, I get to do most of the things I want to do if I don’t do too much of it and, really, the only consequence of my disease that I can discern is that I feel more tired than I‘d like and my muscles ache some. But hey, I’m 65 years old now. Maybe I should feel more tired that I used to.

And that’s all for now. I’ll be back when I learn more about what’s coming my way in the next few months or so.

Dave

***As I start yet another chapter in my battle against leukemia, I am reminded of this quote: --“It is never too late to start. It is always too soon to quit.”—Norma R. Lineberger--Norma worked for the Legal Defense and Education Foundation, and died of leukemia in September 2009.